Transcript ICU Case Presentation

The missing platelets…
where did they go?
Hilary Rowe, BScPharm
VIHA Pharmacy Resident 2009-10
Intensive Care Unit Rotation
April 13, 2010
Outline
•
•
•
•
•
•
•
Objectives
Patient Case
Background
Clinical Question
Review of Evidence
Recommendation
Monitoring
Objectives
• Be able to list the 4 SIRS criteria
• Review pathophysiology for HIT, DIC &
thrombocytopenia in sepsis
• Name 2 risk factors for
thrombocytopenia in the ICU
• Quantify the risk of thrombocytopenia
from Sepsis
Mrs. DG
• ID: 75 yo Female, ht 166cm, wt 65kg
• CC: April 6th- arrived at ER with family;
weakness, ↓ oral intake, difficulty
speaking
• HPI: 4 days of abdominal pain, bloating &
nausea
• ICU Vitals: Temp 359, HR 120, RR 18,
MAP <49, BP 95/60 mmHg, APACHE II
=28
Mrs. DG
•
•
•
•
PMHx: Hypertension, Osteoarthritis
Meds PTA: Losartan 50mg od
Allergies: NKA
SH: From Saskatchewan-on vacation,
2-3 glasses of wine/day, non-smoker
Review of Systems
System
Findings
Medications
CNS
&
Psych
•Pain
•Sedation
•Coma score 3 (no eye
opening, response to
verbal command or motor
response)
•Delirium
•Hydromorphone
infusion
0.1mg/hr
•Midazolam
Infusion 1mg/hr
•Haloperidol
2-10mg IV as
directed prn
Review of Systems
System Findings
Medications
HEENT •OG tube
•ETT
•Chlorhexidine
0.1% bid oral
care
Resp
•Ventilated- rate 20, peep 8
•Salbutamol
FiO2=55%, TV 550, Sats 95% 8-12 puffs q4h
•ACVC: Assist/Control with
& prn
set volume: senses breaths
but has minimum set rate, all
breaths fully ventilator
assisted
Review of Systems
System Findings
Cardio BP-120/60 on therapy
MAP 67-73
HR-120
Rhythm-NS
Medications
•Norepinephrine
0.8mg/kg/min
•Vasopressin
0.6units/hr
•Dobutamine
2.5mg/kg/min
•Hydrocortisone
10mg/hr
Review of Systems
System Findings
GI
Liver
•Ascities-1600 cc fluid
tapped
•Tender to touch left side
•Alb=16↓
•ALT=58↑
•AST=87↑
•Tbili=33↑
•GGT 18N
•INR 1.1↑, PTT 60↑
Medications
•Docusate 200mg
•Ranitidine 50mg
IV q12h
•Albumin 25%
100mls tid x 1 day
Review of Systems
System
Findings
Medications
GU
•SrCr 417
•eGFR 9
•Urosepsis
•Urine output 15cc/6h
•BG 7th
-0900 6.6
-1630 7.4
-2100 9.3
-0200 10.1
•Pen G 2 Million
Units q8h
•Cipro 400mg IV
q24h
Endo
Insulin regular
CCIIP
Review of Systems
System Findings
Heme •WBC 3.8↓, RBC 4.05,
Hgb 126, Hct 0.36, MCV
90, RCDW 12.8, Plt 85↓,
Neuts 2.32, Lymph 0.11↓,
th
•Plts dropped April 7
Medications
•Drotrecogen Alfa
24mcg/kg/hr 96hrs
•Heparin D/C’d 7th
•SCD’s started
Fluids •Na 136
& Lytes •K+ 4.4
•Cl110
•CO2 14↓
•PO4 1.51↑
CaCl 1g IV < 1.13
KCl 20mmol in
SWFI IV prn
NaHCO3- IV
continuous
Review of Systems
System Findings
Medications
C&S
•Blood- Gram + cocci in chains
•Fluid-brown & turbid, 2+
polymorphs, 2+ gram + cocci
•Urine-Streptococcus pyogenes
Blood
gases
•pH=7.27↓
•CO2=27↓
•HCO3-=14↓
•pO2=105↑
•Metabolic acidosis with partial
compensation
Review of Systems
System
Nutrition
Findings
Medications
•Thiamine 100mg IV
od x 3 d
•Folate 5mg IV/PO
od
•MVI I IV then
Replavite po od
•Vit D 2000 units od
SIRS
• Presence of two or more of:
• Temperature < 36 °C or > 38 °C
• Heart rate > 90 beats per minute
• Respiratory rate > 20 breaths per minute or a
PaCO2 less than 32 mm Hg
• White blood cell count < 4 × 109 cells/L or >
12 × 109 cells/L), or greater than 10% bands
 DG Temp 359, HR 120, WBC 3.8 × 109 cells/L
Medical Problems List
• Septic Shock-Urosepsis origin
• Acute Renal Failure
• Thrombocytopenia ?
1. HIT
2. DIC
3. Sepsis
4. Drug cause- Drotrecogen alfa
• Ascites
• ARDS (Pa02/FiO2=190)
DRP’s
• DG is at risk of neurotoxicity (confusion,
delirium, myoclonus) secondary to a
toxic metabolite of hydromorphone in
renal failure and would benefit from reassessment of her pain and sedation
therapy
• DG is at risk of side effects (confusion)
from ranitidine secondary to too high of
a dose in acute renal failure
DRP’s
• DG is at risk of a bleed secondary to
having thrombocytopenia and being on
APC and would benefit from reassessment of her therapy
Thrombocytopenia
9
• Defined as < 100 x 10 platelets/L
• Most common ICU causes
– Sepsis & DIC
• April 7th
9
– 03:22 85 x 10 platelets/L
– 08:30-clumped, 15:30-19C, 22:00 13C
th
• April 8
– 6:10 13C, 17:35 8C
Clinical Question
Rounds
• Could Xigris, DIC, Sepsis, HIT or a
medication error have caused the
thrombocytopenia and can we tell which
one is the culprit?
HIT
• Heparin can combine with a heparin-binding
protein (platelet factor 4) and make an antigenic
complex that causes IgG antibodies to be made
• Antibodies bind platelets and cause aggregation
= platelet consumption and thrombosis
• >50% ↓in platelets 5-10d after 1st exposure
• 5-10% get a redness around sc site
• 25% get systemic reactions if given IV-fever,
chills, ↑ RR, ↑ HR, SOB
DIC & Sepsis
• Gram + & – organisms cause excessive activation of
the clotting cascade
– Platelets are consumed
– Results in thrombocytopenia
• In severe sepsis microvasculature is damaged by
poor perfusion, hypoxia, stasis & acidosis
– Platelets adhere to damage
– Causes activation of platelets & aggregation
– Leads to more platelet consumption
DIC
Points
Plt x 109/L
0
1
2
>100
>50
<50
D-dimer mg/L
<1
1-5
Fibrinogen g/L
>1
<1
Prothrombin Index%
>70
40-70
<40
•>5 points is required to consider DIC
•DG has a score of 7 + some points for
INR >1
3
>5
Lee et al. Singapore Med J 1993
Design Prospective study of illness severity scoring with
the APACHE II system, started in 1991
•Patients admitted to Medical ICU
P
•107 patients mainly Chinese
I
•Patients with Sepsis
C
•Patients without Sepsis
O
•Assess the relationship between clotting
abnormalities, APACHE II and sepsis
•Determine if organism played a key role
Lee et al. Singapore Med J 1993
DG’s APACHE II= 28, Platelets 85 x 109/L
Lee et al. Singapore Med J 1993
Lee et al. Singapore Med J 1993
DG had Streptococcus pyogenes
Lee et al. Singapore Med J 1993
Summary
• Thrombocytopenia (57%) and DIC
(35%) are common in sepsis
• Thrombocytopenia presents early in
sepsis and is a predictor of mortality,
independent of APACHE II for Sepsis
• Patients died of multi-organ failure not
blood loss from thrombocytopenia
Clinical Question
P
75 year old female with Septic Shock
I
Xigris 24mcg/kg/hr
C
No therapy
O
Risk of thrombocytopenia
Time to onset of thrombocytopenia
Risk of clinically significant bleed
Benefit of Xigris
•6.1% ARR (NNT=16, RRR 19.4% P=0.005)
in all cause mortality
•Due to reduction in refractory septic shock,
respiratory failure and improvement in
cardiac and respiratory function
Bernard et al. Critical Care 2003
Review of 7 studies- (2 controlled, 3 openDesign
label & 2 compassionate use studies)
•Patients with severe sepsis
P
I
C
O
•24ug/kg/hr x 96 hr of Drotrecogen Alfa
•Saline or 0.1% albumin in saline or no
comparator
•28 day all cause mortality
•Serious bleeding during & post infusion or by
procedural cause
•Serious bleeding by site of hemorrhage
•Risk of fatal bleeding event
Bernard et al. Critical Care 2003
Inclusion:
•Known or suspected infection with SIRS
•Presence of acute organ dysfunction
Exclusion:
•At high risk of serious bleed
•Severe thrombocytopenia (plts < 30 x 109/L)
•Taking antiplatelet medications
•Receiving systemic heparin anticoagulation
Bernard et al. Critical Care 2003
Mortality rate
• Controlled trials 25.2% (236/940; 95% CI
22.4-28)
• Open-label studies 25.2% (398/1578; 95% CI
23.1-27.4)
• Compassionate use 26.1% (70/268; 95% CI
21-31.8)
• Clinical trials 25.3% (704/2786; 95% CI 23.726.9)
• Placebo 31% (273/881; 95% CI 28-34.2)
Bernard et al. Critical Care 2003
•58/79 SBE during infusion were considered related
to the drug (2.1%; 58/2786)
•8/69 SBE post infusion were considered related to
the drug (0.3% of all treated patients)
Bernard et al. Critical Care 2003
•22/53 (42%)
patients who
experienced a SBE
during the infusion
period had
thrombocytopenia
Bernard et al. Critical Care 2003
• High proportion of SBE was due to
invasive procedures
• 58/148 SBE’s were due to procedures
in the drotrecogen alfa group
• PROWESS trial
– 53.5% (16/30) in drotrecogen alfa group
vs. 23.5% (4/17) in placebo group had a
SBE due to a procedure
Bernard et al. Critical Care 2003
•Non ICH SBE with fatal outcome
-3 events in drug group during infusion
-1 involved thrombocytopenia
(19x109/L) and PTT >150 sec
Bernard et al. Critical Care 2003
Bernard et al. Critical Care 2003
Summary:
• Heparin exposure
– 75% of patients in PROWESS trial were exposed
to heparin, 11/18 with SBE had used heparin
– 14/49 in open-label trials and 3/10 in
compassionate use trials who had SBE were
exposed to heparin
• SBE were highest on day 1
–
–
–
–
56% were procedure related
12 non-procedure related events occurred
9 had platelets < 30 x109/L
3 had an INR > 2
Bernard et al. Critical Care 2003
• Most serious ADR is bleeding
• NNH=66 in PROWESS (3.5% SBE with
therapy vs. 2% with placebo)
• Bernard et al. found SBE rate to be
5.3% overall in the 7 trials assessed
Bernard et al. Critical Care 2003
Conclusion
• Bleeding occurs most often on day 1 of
infusion
• Occurs most often with procedures
• ICH during infusion is associated with
severe thrombocytopenia or meningitis
• Therapy should be stopped if platelets <
< 30 x109/L
Who was the culprit
th
• Xigris was started April 6 at 23:15 and
platelets declined April 7th by 08:30
st
– SBE occurred most often on 1 day of
infusion-associated with thrombocytopenia
– Timing seems appropriate
• Patient is also at risk of sepsis induced
thrombocytopenia & DIC
• Naranjo ADR scale= 3, possible
What do you think?
Goals of Therapy
Patients Goals
• Full code
Team Goals
• Cure urosepsis
• Improve renal function
• Wean patient from ventilator
• Prevent Bleeding
• Prevent Clotting
• Decrease morbidity & mortality
• Minimize adverse drug events
Therapeutic Options
•Continue Drotrecogen Alfa
Discontinue Drotrecogen Alfa
•Continue Heparin
Discontinue Heparin
Start Sequential compression devices
•Give Platelets
Monitoring
Adverse Events
Monitor
Who
When
How Long
INR & PTT
Dr. & Rx
Each
morning
Daily while
in ICU
Platelets
Dr.
Daily
Daily while
in ICU
Bleeding-ETT,
urine, bowel,
vomit, nose…
Dr. &
Nurse
QID
Daily while
in ICU
Monitoring
Efficacy
Monitor
Who
When
How Long
Ventilation
Dr., RT, Rx
Daily
While in ICU
Use of
vasopressors
Dr., RN, Rx Daily
While in ICU
Need for
Dr., Rx
hydrocortisone
Daily
While on
vasopressors
Questions?
References
• Bernard GR, Macias WL, Joyce DE et al. Safety assessment of
drotrecogen alfa (activated) in the treatment of adult patients
with severe sepsis. Critical Care 2003;7:155-63.
• Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of
recombinant human activated protein C for severe sepsis.
NEJM 2001; 344 (10): 699-709.
• Lee KH, Hui KP, Tan WC. Thrombocytopenia in sepsis: a
predictor of mortality in the intensive care unit. Singapore Med J
1993;34:245-46.
• Marino PL. The ICU Book 3rd ed. Philadelphia: Lippincott
Williams & Wilkins; 2007. page 684-7.
• Naranjo CA, Busto U, Sellers EM et al. A method for estimating
the probability of adverse drug reactions. Clin Pharmacol Ther
1981; 30(2): 239-45.